Redox active or thiol reactive? : optimization of rapid screens to identify less evident nuisance compounds

Proj, Matic (author), Knez, Damijan (author), Sosič, Izidor (author), Gobec, Stanislav (author)

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.

• Language: English
• Keywords: redox, covalent, screening, hits, PAINS, assays
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 1733-1742
• Numbering: Vol. 27, no. 6
• PID: 20.500.12556/RUL-139090
• UDC: 615.4:54
• ISSN on article: 1359-6446
• DOI: 10.1016/j.drudis.2022.03.008
• COBISS.SI-ID: 100881923
• Publication date in RUL: 30.08.2022

Record is a part of a journal

• Title: Drug discovery today
• Shortened title: Drug discov. today
• Publisher: Elsevier
• ISSN: 1359-6446
• COBISS.SI-ID: 1216021

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: redoks, kovalentni presejalni pregled, testi, farmacevtska kemija, zdravila

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin